Cited by 259Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

Understanding the Role of Systemic Inflammation in Alzheimer’s Disease

Walker, Keenan A., Ficek, Bronte N., Westbrook, Reyhan·2019·ACS Chemical Neuroscience

Abstract

Human and animal studies suggest that inflammation occurring outside the central nervous system (systemic inflammation) may play a key role in promoting neurodegeneration, Alzheimer's disease pathology, and cognitive decline in older adults. Systemic inflammation, which is marked by increased blood levels of circulating proinflammatory cytokines and chemokines, may occur as a result of events such as infection, chronic disease, and physical and psychological stress, but may also occur outside the context of these conditions as a result of subclinical processes such as cellular senescence. Proinflammatory cytokines within the body can promote a proinflammatory environment in the central nervous system by crossing the blood-brain barrier, signaling through endothelial cells or circumventricular organs, and by stimulating the vagus nerve, which signals the detection of inflammatory proteins via direct afferent connections to the brain stem. Through each of these routes, systemic inflammation is believed to induce reactive, proinflammatory microglia and astrocytic phenotypes which can promote tau hyperphosphorylation, β-amyloid oligomerization, complement activation, and the breakdown of neurotransmitters into potentially harmful bioactive metabolites. Together, these molecular changes are believed initiate or exacerbate neurodegenerative processes that can eventually lead to cognitive decline and dementia in vulnerable older adults.

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Crossref · 10.1021/acschemneuro.9b00333

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Authors
Walker, K. A., Ficek, B. N., & Westbrook, R.
Affiliations
Johns Hopkins University (US)
Corresponding author
Walker, Keenan A.
Venue
ACS Chemical Neuroscience
Published
2019-06-26
Volume
10
Issue
8
Pages
3340-3342
ISSN
1948-7193 (ISSN-L)
OpenAlex
W2954317829
Cited by
259
References
5
Citations by year
2026: 26 · 2025: 37 · 2024: 59 · 2023: 43 · 2022: 29 · 2021: 47 · 2020: 15 · 2019: 3
Type
journal article
Language
en
Open access
closed
Locations
  • ACS Chemical Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (AG027668)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
systemic inflammation, Alzheimer's disease, neuroinflammation, inflammatory cytokines, chemokines, blood-brain barrier, vagus nerve, microglial activation, astrocytes, tau hyperphosphorylation, amyloid oligomerization, complement activation, cellular senescence, cognitive decline, dementia, older adults
MeSH terms
Alzheimer Disease, Animals, Humans, Inflammation, Neuroimmunomodulation

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